The Louisiana State University Health Sciences Center (LSUHSC) New Orleans Comprehensive Alcohol- HIV/AIDS Research Center (CARC) is a multi-institutional, multidisciplinary team of scientists from LSUHSC, the Tulane National Primate Research Center (TNPRC) and Tulane University School of Public Health and Tropical Medicine (TSPHTN), with a research focus on the interaction of alcohol use disorders (AUD), simian and Human Immunodeficiency Virus (SIV/HIV), and Antiretroviral Therapy (ART) in non- human primates (NHP) and human subjects. This renewal application showcases our accomplishments and defines the evolution and expansion of our research strategy to now include clinical studies that will facilitate bi-directional translational investigation of AUD, HIV/AIDS, and ART comorbid conditions and their exacerbation in an underserved cohort of persons living with HIV/AIDS (PLWHA). The CARC will provide and enhance the necessary infrastructure to perform longitudinal pre-clinical and clinical translational studies on the interaction of AUD with HIV/AIDS. An Administrative Core will provide oversight for all CARC activities. Five Research Components (RC), will focus on rarely studied female rhesus macaques (RC1 and RC2), and a cohort of underserved PLWHA a large percent being women (RC3, RC4, RC5). RC1 will study chronic binge alcohol (CBA)-mediated alterations in female genital mucosa. RC2 will investigate the mechanisms of altered muscle and adipose functional phenotype associated with metabolic dysfunction. RC3 will examine the interaction between the microbiota, and inflammaging in PLWHA with AUD. RC4 will identify the clinical associations between AUD and HIV-associated cancer pathogenesis. RC5 will study the combined impact of AUD and chronic social and environmental stress on disease-related biological outcomes among PLWHA. Two Resource Cores -Experimental and Analytical- will provide support for studies proposed by all RC and Pilot Projects. An Information Dissemination Core will promote training and accelerate the translation and dissemination of CARC research findings to the clinical arena. A Pilot Project Core will promote the development and exploration of novel research investigations, thereby maximizing the unique scientific opportunities provided by the CARC. The CARC will continue to leverage and synergize with existing resources including the Louisiana Clinical and Translational Science Center, Minority-Based Community Clinical Oncology Program, and the LSUHSC Stanley S. Scott Cancer Center. Together, access to a unique HIV+ population in a Southeast urban region, the established expertise of CARC investigators in biomedical and behavioral research, state of the art research facilities, outstanding scientific environment, and strong institutional support will ensure that the proposed activities within the LSUHSC CARC will continue to be successful as we evolve and mature in our approach to understanding the comorbid consequences of AUD, HIV/SIV, and ART in PLWHA.